Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome

Abstract

This study evaluates the effect of an oral contraceptive containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on hormone dynamics, clinical signs of androgenization and ovarian size in patients with polycystic ovary syndrome (PCOS). Forty-six patients with PCOS were treated with Diane-35 for between 9 and 30 cycles without interruption (a total of 688 cycles). Clinical and hormonal evaluations were performed before treatment and every 3rd cycle during the treatment period while ultrasonographic assessment of ovaries was carried out every 6th cycle. A highly significant decrease in the LH/FSH ratio (p less than 0.001) as well as testosterone levels (p less than 0.001) was noticed after the 3rd cycle of Diane-35 administration. The mean serum androstenedione level decreased significantly (p less than 0.025) after the 3rd cycle, and showed a lowering trend thereafter. A significant reduction in serum DHEA-S levels was observed after the 6th cycle of treatment and they also showed a subsequent lowering trend. A highly significant increase in SHBG concentrations (p less than 0.001) was noticed after the 3rd cycle. Most of the patients noticed improvement in hirsutism between the 8th and 12th cycles of treatment. Mean ovarian size decreased significantly (p less than 0.001) after the 6th cycle, the normal size being reached after the 12th cycle of treatment. After the 4th cycle treatment was discontinued in 1 patient due to secondary amenorrhea, and in another 3 patients because of an increase in diastolic blood pressure. In a few patients side-effects such as weight gain, breast tenderness and mood changes in mild form were reported. Three out of 7 patients conceived in the 2nd or 3rd cycle after discontinuing Diane-35 therapy. The results of this study show that a combination of low-dose estrogen and cyproterone acetate (Diane-35) successfully reduces the hormonal disturbances which characterize PCOS. Apart from the normalization of the hormonal profile and the decrease in ovarian size, beneficial effects of Diane-35 were also observed on acne, hirsutism and regulation of the menstrual cycle. Favourable effects were also seen in terms of the pregnancy rate after discontinuation of Diane-35 therapy.